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Moleculebiological analysis of HLA class II in autoimmune hepatitis.

自身免疫性肝炎HLA II类的分子生物学分析。

基本信息

批准号：
03454227
负责人：
KIYOSAWA Kendo
金额：
$ 4.03万
依托单位：
Shinshu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

项目摘要

1. To investigate the association between autoimmune hepatitis and HLA alleles in Japanese patients, serological typing and class II genotyping were performed using the polymerase chain reaction-restriction fragment length polymorphisms(PCR-RFLP)method. Serologicaltyping showed that HLA-B54, -Dr53, and -DQ4 were significantly associated with autoimmune hepatitis (88.7%). In PCR-RFLP typing, the frequency of Dw between the patients and thecontrols who were DR4-positive. The significant increase observed in DQA1**0301 and DQB1**0401 was explained by a linkage disequilibrium with DR4. Six DR4-negative patients had DR2, but there was no significant difference in the frequency of the DR2-positive controls. No DQB1 allele was significantly associated with autoimmune hepatitis. These findings suggest that the basic amino acid at position 13, which is present only on the DR4 B1 molecules (Arg on DR2 and His on DR4), contributes to the susceptibility to autoimmune hepatitis among the Japanese.2 … More . We clarified the clinical and immunogenetical differences between patients with autoimmune hepatitis (AI-CAH), and patients with type C chronic active hepatitis(C-CAH) and type B chronic active hepatitis (B-CAH) who were positive for autoantibodies and hyperglobulinemia. While histories of blood transfusion, intravenous drug abuse and tattoo were seen frequently in patients with type C-CAH, they were rare in patients with AI-CAH.The severe subjective symptoms including anorexia, lethargy, icterus, high fever and extrahepatic manifestations, and severe abnormality of biochemical data were seen in AI-CAH.HLA-DR4 was the most frequently associated with AI-CAH(89%) and 6 DR4-negative patients were positive for DR2. HLA-DNA typing showed that there was no significant difference in the frequency of DR4-associated Dw-alleles between the patients and controls who were positive for DR4. These findings suggest that the basic amino acid at position 13, which is present only DR2 and DR4-B1 molecules, may contribute to the susceptibility to autoimmune hepatitis of Japanese. Thus, we conclude that AI-CAH is a genetically restricted disease and different from C-CAH which is a viral infectious disease. Less

1.为了探讨日本患者自身免疫性肝炎与HLA等位基因的关系，采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行血清学分型和II类基因分型。血清学分型显示HLA-B54、-Dr53和-DQ4与自身免疫性肝炎显着相关（88.7%）。在PCR-RFLP分型中，DR4阳性的患者和对照之间的Dw频率。 DQA1**0301 和 DQB1**0401 中观察到的显着增加可以通过与 DR4 的连锁不平衡来解释。 6 名 DR4 阴性患者患有 DR2，但 DR2 阳性对照的频率没有显着差异。没有 DQB1 等位基因与自身免疫性肝炎显着相关。这些发现表明，仅存在于 DR4 B1 分子上的第 13 位碱性氨基酸（DR2 上的 Arg 和 DR4 上的 His）导致日本人对自身免疫性肝炎的易感性。2 … 更多。我们阐明了自身免疫性肝炎（AI-CAH）患者与自身抗体阳性且高球蛋白血症的丙型慢性活动性肝炎（C-CAH）和乙型慢性活动性肝炎（B-CAH）患者之间的临床和免疫遗传学差异。 C-CAH患者常有输血、静脉吸毒、纹身史，而AI-CAH患者则少见。AI-CAH患者有厌食、嗜睡、黄疸、高热、肝外表现等严重主观症状，生化数据严重异常。其中HLA-DR4与AI-CAH最常见（89%），6 DR4 阴性患者 DR2 呈阳性。 HLA-DNA 分型显示 DR4 阳性患者和对照者之间 DR4 相关 Dw 等位基因的频率没有显着差异。这些发现表明，仅存在于DR2和DR4-B1分子的13位碱性氨基酸可能与日本人对自身免疫性肝炎的易感性有关。因此，我们得出结论，AI-CAH是一种遗传限制性疾病，与C-CAH不同，C-CAH是一种病毒感染性疾病。较少的